A Versatile Approach to Synergistically Combine Physical Barriers and Bioactive Agents for Intrauterine Adhesion Prevention

Abstract Intrauterine adhesions (IUA) are characterized by fibrotic repair and partial or complete occlusion of the uterine cavity, resulting from endometrial damage. The occurrence of IUA can adversely affect the reproductive and physiological health of women. Developing a delivery platform capable of loading various bioactive agents to achieve personalized treatment strategies can significantly enhance IUA therapy. In this study, cryopolymerization is employed to fabricate an antifouling porous scaffold (GNP) with shape memory properties, serving as a delivery vehicle for bioactive agents. Both in vitro and in vivo experiments demonstrate that GNP can incorporate multiple bioactive agents (penicillin‐streptomycin (PS), stem cell exosomes (Ex) and N‐acetylcysteine (NAC)), and promote their sustained retention. Based on the core factors of adhesion formation, the antioxidant NAC is chosen as a model agent combined with GNP. In the rat IUA model, NAC‐loaded GNP (P150N) modulates the endometrial microenvironment through its antioxidant, anti‐inflammatory, and anti‐fibrotic actions. P150N effectively facilitates endometrial regeneration, reduces adhesion formation, and significantly increases embryo implantation rates. Additionally, proteomics analysis reveals that the P150N significantly downregulates proteins associated with inflammation, oxidative stress, and fibrosis, while upregulating those involved in cell proliferation. Overall, this work presents a versatile platform, offering a potential personalized therapeutic strategy for IUA prevention.